Studies concerning the health effects of groundwater contaminants have been focused primarily on cancer as an endpoint. In the present studies, bone marrow parameters were monitored in mice exposed to 0, 1, 5, and 10% of a chemical mixture in drinking water for 17 days or up to 32 weeks. The mixture consisted of 25 common groundwater contaminants frequently found near toxic waste dumps as determined by EPA surveys. Mice exposed to 5 and 10% of stock solution for 15.5 weeks showed suppression of granulocyte-macrophage progenitor cells and erythroid precursors with few or no effects on body weight, histopathology and peripheral blood counts. Mice were allowed to recover for 10 weeks at which time they received whole body irradiation. Previously chemical-treated mice were more sensitive to irradiation than untreated controls. Furthermore, synergistic effects of chemical and irradiation were demonstrated by continuing chemical exposure with multiple irradiation. The effect became more pronounced following multiple irradiation and the recovery of progenitor cells occurred more slowly. Thus, chemical exposure caused a significant residual marrow damage that was not apparent with routine hematological or pathological techniques, but could be demonstrated by subsequent irradiation. These results suggest that long-term exposure to highly contaminated groundwater may present a subtle risk to the hematopoietic stem cells.